Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning

作者: Fred Fändrich , Xiongbin Lin , Gui X. Chai , Maren Schulze , Detlev Ganten

DOI: 10.1038/NM0202-171

关键词: ToxicityTolerance inductionEmbryonic stem cellGenetic enhancementImmunologyTransplantationStem cellHaematopoiesisBiologyImmune systemGeneral Biochemistry, Genetics and Molecular BiologyGeneral Medicine

摘要: Hematopoietic stem cells have been successfully employed for tolerance induction in a variety of rodent and large animal studies. However, clinical transplantation fully allogeneic bone marrow or blood-borne is still associated with major obstacles, such as graft-versus-host disease cytoreductive conditioning-related toxicity. Here we show that when rat embryonic cell-like WKY origin are injected intraportally into MHC-mismatched DA rats, they engraft permanently (>150 days) without supplementary host conditioning. This deviation potentially alloreactive immune response sets the basis long-term graft acceptance second-set transplanted cardiac allografts. Graft survival was strictly correlated state mixed chimerism, which required functional thymic competence. Our results provide rationale using preimplantation-stage vehicles gene therapy acceptance.

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